Development of continuous enzymatic production using a continuous oscillatory baffled reactor

随着对可持续性和减少工业过程碳足迹的关注，生物催化越来越被视为解决这些问题的一种方法。此外，酶促生产的材料还可以受益于更少的下游加工步骤，并且可以具有更高的质量。然而，通常在较温和的反应条件和较长的反应时间之间存在权衡，特别是在大规模进行时。因此，在不影响产量的情况下实现生物催化反应的技术对于禾大实现关键化学药品的绿色生产至关重要。连续振荡挡板反应器（COBR）被认为是一种可用于优化酶促反应同时保持产量的技术。基于禾大在生物催化反应方面的现有知识以及与倪教授在COBR中开发新型连续生产的经验，该BBSRC/禾大博士项目旨在建立对药物反应过程、反应动力学、影响动力学的参数和反应转化率的基本理解;建立与流体力学耦合的动力学模型，预测反应转化率和反应器性能;评估市售酶以及禾大单独开发的酶和与其他酶联合开发的酶的活性;评估使用游离酶与负载酶的成本影响，并设计和测试连续去除和回收酶的创新方法。

With an increased focus on sustainability and reducing the carbon footprint of industrial processes, biocatalysis is increasingly seen as a solution to these problems. Furthermore, material produced enzymatically may also benefit from fewer downstream processing steps and may be of higher quality. However, there is often a trade-off between milder reaction conditions and longer reaction times, particularly when done at scale. Therefore, technologies that could allow biocatalytic reactions to occur without having to compromise on throughput are crucial in enabling Croda to establish greener production of key pharmaceutical chemicals.The Continuous Oscillatory Baffled Reactor (COBR) has been identified as a technology that could be used to optimise enzymatic reactions whilst maintaining throughput. Building upon Croda's prior knowledge in biocatalytic reactions and the development of novel continuous production in the COBR with Prof Ni previously, this BBSRC/Croda PhD project aims to establish the fundamental understanding of a pharmaceutical reaction process, the reaction kinetics, parameters affecting kinetics and reaction conversion; to build a kinetic model that is coupled with fluid mechanics in order to predict reaction conversion and reactor performance; to assess the activities of commercially available enzymes as well as these that were developed by Croda both on their own and in combination with others; to evaluate the cost implications of using free enzyme(s) versus supported enzyme(s) and to design and test innovative means of removing and recovering of enzyme continuously.